The objective of these studies is to determine how renal function is regulated by metabolic and hormonal mechanisms. The quantitative and qualitative relationships among renal substrate uptake, the metabolic fates of substrates in the kidney and renal function are being determined. In this context whether the regulatory role of hormones such as insulin, parahormone, ADH, etc. on renal function is obligatorily linked to metabolic phenomena or can occur without a change in renal metabolism is being probed. The studies are being done primarily with the isolated perfused rat kidney, where the variables of substrate availability, substrate concentration and hormone concentration can be varied over ranges not possible in vivo. Kidneys for perfusion are obtained from normal rats and from rats whose physiological state has been altered (e.g., chronic acidosis, or streptozoticin diabetes, etc.). When appropriate, studies are also being done in the intact rat or dog. Whether the metabolic pathways by which substrates are utilized change or whether there is a change in substrate affinity when renal function is changed is being probed by measuring the rates of decarboxylation and rates of conversion of substrates to new products (e.g., glucose or fat). In contrast to measurements of total renal O2 uptake alone, measurement of the specific changes in either substrate uptake or pathway of metabolism would permit a more accurate estimate to be made of the energy requirements for certain renal functions. The hypothesis that there are changes in rate of formation of certain products in the kidney when ECF-pH or volume is changed is being tested. Evidence has been obtained that lactate and glucose each supports certain renal functions (GFR, Na ion reabsorption) to different degrees. BIBLIOGRAPHIC REFERENCES: Cohen, J.J., Y.J. Kook and J.R. Little. Substrate-limited function and metabolism of the isolated perfused rat kidney: Effects of lactate and glucose. J. Physiol. 266: 103-121, 1977. Cohen, J.J., L.S. Merkens, C.M. Gregg. Selective support of renal functions by specific substrates. Invited paper for presentation at the Round-Table Discussion on "Metabolism and Functional Interrelationships in Kidney Cells", International Cong. of Physiol. XXVII, Paris, France, July 1977.